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Thymidine phosphorylase

thymidine phosphorylase, PD-ECGF

This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008] (from
NCBI)

Various approaches have been used to improve the efficacy of 5-FU including inhibition of its degradation enzyme dihydropyrimidine dehydrogenase (DPD) such as S1, UTF, use of 5-FU pro-drug capecitabine to exploit thymidine phosphorylase (TP) and supplementation of reduced folate acid to increase cytotoxicity.

Capecitabine, which is commonly used for metastatic breast cancer in different settings, is an inactive prodrug that takes advantage of elevated levels of thymidine phosphorylase (TP), a key enzyme that is required for its conversion to 5-fluororacil, in tumors.

TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models.

Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase.

PURPOSE: To evaluate the clinical activity and toxicity of capecitabine plus irinotecan as first-line therapy for patients with metastatic colorectal cancer (mCRC), and to describe the association of expression of thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) with antitumor activity.

Furthermore, the prognostic value of molecular biomarkers, such as thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD), all of which are involved in the FU metabolism, is unknown in neoadjuvant settings.